The research program in Hematopoietic Cell Transplantation and Immune Reconstitution (Program 08) focuses on elucidating basic biological principles of hematopoietic cell transplantation (HCT) and furthering the treatment of patients with life-threatening hematologic malignancies. The major theme of the Program is the discovery of immunology and stem cell biology principles that can be translated into innovative HCT based therapies. Our goals are: To gain fundamental insights into the cellular basis of hematopoietic stem and progenitor cell engraftment. To explore the basic biology of graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) reactions in the context of transplantation. To develop strategies to improve immune reconstitution. To translate promising concepts developed in pre-clinical studies to the clinic. Using a highly interactive group of investigators with a rich array of animal models incorporating the latest techniques of cell biology, imaging, genetics and array technologies we will explore in animal models and in patients the biological principles that govern these immune-based reactions and develop strategies to improve outcomes for our patients. These concepts could also have an impact on a variety of other clinical situations, such as for the treatment of autoimmune disorders and induction of solid organ transplantation tolerance. Using the principles of translational science whereby model systems are developed in the laboratory and concepts are tested in the clinic in a bi-directional fashion, analyzing patients' samples will allow us to test important concepts of HCT and follow critical leads established in research laboratories to the treatment of patients with hematologic disorders.